• Disease Overview
  • Synonyms
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Disorders with Similar Symptoms
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
  • References
  • Programs & Resources
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Pachydermoperiostosis

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Last updated: December 01, 2021
Years published: 1992, 2000, 2005, 2008, 2021


Acknowledgment

NORD gratefully acknowledges Sunaina Kapur, MMSc, NORD Editorial Intern from the Emory University Genetic Counseling Training Program and Cecelia A. Bellcross, PhD, MS, CGC, Associate Professor, Director, Genetic Counseling Training Program, Emory University School of Medicine, for assistance in the preparation of this report.


Disease Overview

Pachydermoperiostosis, also called primary hypertrophic osteoarthropathy (PHO) is a rare genetic condition. The three main features are large finger tips (clubbing), thickening of the skin of the face (pachydermia) and extra sweating (hyperhidrosis). It typically starts during childhood or adolescence, often around the time of puberty, and progresses slowly for about ten years.

Pachydermoperiostosis is the complete form of PHO where there is also unusual thickness of the skin (pacydermia). There are also two incomplete forms, one with isolated bone problems and skin changes, and one with pachydermia and minimal or absent new bone growth (periostosis).

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Synonyms

  • primary hypertrophic osteoarthropathy
  • pachydermoperiostosis syndrome
  • Rosenfeld-Kloepfer syndrome
  • Touraine-Solente-Gole syndrome
  • PHO
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Signs & Symptoms

PHO is characterized by problems with the growth of skin and bones. People with PHO usually have coarse facial features with oily, thick, grooved skin on the face, joint pain, large tips of the fingers and toes (clubbing) and extra sweating of the hands and feet (hyperhidrosis).

New bone growth (periostosis), often at the ends of the long bones, causes joint pain. Extra skin on the scalp can be seen that causes deep grooves or ridges (cutis verticis gyrate).These grooves or ridges usually occur during the teen years.

Other symptoms can include swelling or pain of the large joints; drooping eyelids (ptosis); a long-term skin condition that causes dry or moist scales and a yellowish crust (seborrheic dermatitis); ulcers; long eyelashes; occasional diarrhea; swelling of hair follicles related to large open pores of the skin; heart disease present at birth and/or delayed closure of the space between the bones of the skull (fontanelles).

The symptoms vary between individuals, but overall, males tend to have more serious symptoms than females. X-rays can help look at features that are not as noticeable to the naked eye.

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Causes

For most individuals, the diagnosis of PHO is based on the clinical features. It is recognized more often in males than females, as males have more noticeable and severe features. PHO can be inherited, but a non-genetic form has also been described.

Genetic conditions can be inherited in different ways. Individuals typically inherit one copy of a gene pair from their mother, and the other from their father. Genes provide instructions to tell the body how to function. When there is a harmful change (mutation) in a gene it may not function normally leading to unusual features and/or conditions. Autosomal dominant and autosomal recessive inheritance patterns have been reported for PHO.

There are two genes that have been associated with PHO: HPGD and SLCO2A1. Mutations in HPGD are associated with autosomal recessive inheritance and this condition is sometimes abbreviated PHOAR1 or Touraine-Solente-Gole syndrome.

Recessive genetic conditions occur when an individual inherits one non-working gene for the same condition from each parent. If an individual receives one normal gene and one gene with a mutation, the person will be a carrier for the condition and will usually not show symptoms. The chance for two carrier parents to both pass the non-working gene and, therefore, have a child with that condition is 25% with each pregnancy. The chance to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal working genes from both parents is 25%. The chance is the same for males and females.

Parents who are closely related by blood (consanguineous) have a higher chance than unrelated parents to both carry the same non-working gene, which increases the chance to have children with a recessive genetic disorder.

PHO caused by mutations in SLCO2A1 can be dominant or recessive. The recessive form is called PHOAR2. The dominant form is called PHOAD. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to see symptoms of the condition. The non-working gene can be inherited from either parent or can be the result of a new mutation (gene change) in the individual with the condition. The chance of passing the non-working gene from an affected parent to child is 50% for each pregnancy. The risk is the same for males and females. However, with PHOAD, males are more commonly and often more severely affected.

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Affected populations

PHO is a rare disorder that affects males more than females with a ratio of 7:1. This means that for about every 7 males that are diagnosed with this condition, 1 female is diagnosed. However, since females tend to have milder symptoms than males, females may go undiagnosed.

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Diagnosis

The diagnosis of PHO is made based on clinical features, though genetic testing can confirm the diagnosis. Major diagnostic criteria include clubbing of the fingers (digital clubbing) and new bone growth (periostosis).

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Standard Therapies

Treatment

Treatment is mostly aimed at specific symptoms and is supportive. Nonsteroidal anti-inflammatory drugs (NSAIDs, such as Advil), colchicine, or corticosteroids can be taken to decrease bone and joint pain.

Vagotomy, a surgical procedure in which certain branches of the vagus nerve are cut, may improve joint pain and swelling. Retinoids can be used to treat symptoms that involve the skin. Plastic surgery may be performed to improve facial appearance. Surgery can treat clubbing of the fingers.

Genetic counseling may be helpful for patients and their families.

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Clinical Trials and Studies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222 TTY: (866) 411-1010 Email: prpl@cc.nih.gov

Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/

For information about clinical trials sponsored by private sources, contact: www.centerwatch.com

For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/

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References

TEXTBOOKS

Fauci AS, Braunwald E, Isselbacher KJ, et al., eds. Harrison’s Principles of Internal Medicine. 20/E McGraw-Hill Companies. New York, NY; 2018.

Griffiths C, Barker J, Bieiker T et al. Rook’s Textbook of Dermatology. 9th ed. Wiley Blackwell Scientific Publications. London, UK; 2016.

JOURNAL ARTICLES

Xu Y, Zhang Z, Yue H, Li S, Zhang Z. Monoallelic mutations in SLCO2A1 cause autosomal dominant primary hypertrophic osteoarthropathy. J Bone Miner Res. 2021 Aug;36(8):1459-1468. doi: 10.1002/jbmr.4310. Epub 2021 May 5. PMID: 33852188.

Marques P, Stelmachowska-Banas M, Collier D, Wernig F, Korbonits M. Pachydermoperiostosis mimicking the acral abnormalities of acromegaly. Endocrine 2020; 67(2): 499–500.

Joshi, A., Nepal, G., Shing, Y.K. et al. Pachydermoperiostosis (Touraine–Solente–Gole syndrome): a case report. J Med Case Reports 2019; 13: 39. https://doi.org/10.1186/s13256-018-1961-z.

Yuan L, Liao RX, Lin YY, et al. Safety and efficacy of cyclooxygenase-2 inhibition for treatment of primary hypertrophic osteoarthropathy: a single-arm intervention trial. J Orthop Translat. 2019;18:109-118.

Wang Q, Ying-he L, Guo-le L, et al. Primary hypertrophic osteoarthropathy

related gastrointestinal complication has distinctive clinical and pathological

characteristics: two cases report and review of the literature. Orphanet Journal of Rare Diseases. 2019;14:297. https://doi.org/10.1186/s13023-019-1264-5

Yuan L, Chen X.,Liu Z, Wu D, Lu J, Bao G, Zhang S, Wang L, & Wu Y.

Novel SLCO2A1 mutations cause gender-differentiated pachydermoperiostosis, Endocrine Connections. 2018; 7(11) 116-1128.

Li SS, He JW, Fu WZ, Liu YJ, Hu YQ, Zhang ZL. Clinical, biochemical, and genetic features of 41 Han Chinese families with primary hypertrophic osteoarthropathy, and their therapeutic response to etoricoxib: results from a six-month prospective clinical intervention. J Bone Miner Res. 2017;32(8):1659-1666.

Lee S, Park SY, Kwon HJ, Lee CH, Kim OH, Rhee Y. Identification of the Mutations in the Prostaglandin Transporter Gene, SLCO2A1 and Clinical Characterization in Korean Patients with Pachydermoperiostosis. J Korean Med Sci. 2016 May;31(5):735-42.

Zhang Z, He JW, Fu WZ, Zhang CQ, Zhang ZL. Mutations in the SLCO2A1 gene and primary hypertrophic osteoarthropathy: a clinical and biochemical characterization. J Clin Endocrinol Metab. 2013;98(5):E923-E933.

Uppal S, Diggle CP, Carr IM, et al. Mutations in 15-hydroxyprostaglandin dehydrogenase cause primary hypertrophic osteoarthropathy. Nature Genet. 2008;40: 789-793.

Castori M, Sinibaldi L, Mingarelli R, Lachman RS, Rimoin DL, Dallapiccola B. Pachydermoperiostosis: an update. Clin Genet. 2005;68(6):477-486.

Pichler G, Eber E, Thalhammer G, et al. Arthralgia and digital clubbing in a child: hypertrophic osteoarthropathy with inflammatory pseudotumour of the lung. Scand J Rheumatol. 2004;33:189-91.

Seggewiss R, Hess T, Fiehn C. A family with a variant form of primary hypertrophic osteoarthropathy restricted to the lower extremities. Joint Bone Spine. 2003;70:230-33.

Levin SE, Harrisberg JR, Govendragaloo K. Familial primary hypertrophic osteo-arthropathy in association with congenital heart disease. Cardiol Young. 2002:12;304-07.

Akdeniz BG, Seekin T. Periodontal and alveolar bone abnormalities associated with pachydermoperiostosis. Periodontal Clin Investig. 2001:23;5-10.

Jajic Z, Jajic I, Nemeic T. Primary hypertrophic osteoarthropathy: Clinical, radiologic, and scintigraphic characteristics. Arch Med Res. 2001;32:136-42.

Silveira LH, Martinez-Lavin M, Pineda C, et al. Vascular endothelial growth factor and hypertrophic osteoarthropathy. Clin Exp Rheumatol. 2000;18:57-62.

Jajic Z, Jajic I, Nemcic T. Hypertrophic osteoarthropathy after cerebrovascular insult. Clin Exp Rheumatol. 2000;18:262.

Demirpolat G, Sener RN, Stun EE. MR imaging of pachydermoperiostosis. J Neuroradiol. 1999;26:61-63.

Friedhofer H, Salles AG, Gemperli I, et al. Correction of eyelid anomalies in pachydermoperiostosis. Ophthal Plas Recontr Surg. 1999;15:137-38.

INTERNET

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. https://www.omim.org/entry/167100?search=167100&highlight=167100 ; https://www.omim.org/entry/259100?search=259100&highlight=259100; https://www.omim.org/entry/614441 Accessed 11/30/21.

Pachydermoperiostosis. Medscape. Updated April 6, 2021. Available at: https://emedicine.medscape.com/article/1075122-overview Accessed 11/27/2021.

Pachydermoperiostosis. Orphanet. Last update Jan 2011. Available at: https://www.orpha.net/consor/cgi-bin/Disease_Search_Simple.php?lng=EN&diseaseGroup=Pachydermoperiostosis Accessed 11/27/2021.

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This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.

Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/

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National Organization for Rare Disorders